Yin Yang 1 is a critical repressor of matrix metalloproteinase-9 expression in brain neurons.
Membrane depolarization controls long lasting adaptive neuronal changes in brain physiology and pathology. Such responses are believed to be gene expression-dependent. Notably, however, only a couple of gene repressors active in nondepolarized neurons have been described. In this study, we show that in the unstimulated rat hippocampus in vivo, as well as in the nondepolarized brain neurons in primary culture, the transcriptional regulator Yin Yang 1 (YY1) is bound to the proximal Mmp-9 promoter and strongly represses Mmp-9 transcription. Furthermore, we demonstrate that monoubiquitinated and CtBP1 (C-terminal binding protein 1)-bound YY1 regulates Mmp-9 mRNA synthesis in rat brain neurons controlling its transcription apparently via HDAC3-dependent histone deacetylation. In conclusion, our data suggest that YY1 exerts, via epigenetic mechanisms, a control over neuronal expression of MMP-9. Because MMP-9 has recently been shown to play a pivotal role in physiological and pathological neuronal plasticity, YY1 may be implicated in these phenomena as well.
Rylski
Marcin
M
Department of Molecular and Cellular Neurobiology, Nencki Institute, Pasteura 3, 02-093 Warsaw, Poland. m.rylski@gmail.com
Amborska
Renata
R
Zybura
Katarzyna
K
Mioduszewska
Barbara
B
Michaluk
Piotr
P
Jaworski
Jacek
J
Kaczmarek
Leszek
L
D000107:Acetylation; D000818:Animals; D001921:Brain / Q000201:enzymology* / Q000378:metabolism; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism*; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism; D011401:Promoter Regions, Genetic; D051381:Rats; D017208:Rats, Wistar; D050986:YY1 Transcription Factor / Q000737:chemistry* / Q000502:physiology*
D006657:Histones; D050986:YY1 Transcription Factor; C494700:Yy1 protein, rat; D020780:Matrix Metalloproteinase 9